Evidence that the SARS-CoV-2 virus is genetically engineered

A scientist argues that the evidence for a “natural” origin for the virus is fabricated. Report: Claire Robinson

An anonymous scientist[1] has published a detailed article arguing that SARS-CoV-2, the virus causing the COVID-19 pandemic, is a genetically engineered lab creation. What’s more, the author argues that the particular bat coronavirus from which SARS-CoV-2 is claimed to have naturally emerged – dubbed RaTG13 – is a fabrication. In other words, the author says the “natural origin” for the virus was made up in a desperate attempt to let those responsible for the lab escape off the hook.

According to the author, the fabrication was perpetrated by Shi Zhengli, director of the Wuhan Institute of Virology (WIV) in China. The WIV is only a few kilometres from the Wuhan seafood and wildlife market that was initially blamed for the outbreak. Zhengli has been dubbed by the media “the bat woman” for her role in collecting bat viruses from the wild for her “gain-of-function” research.

“Gain-of-function” research seeks to make viruses more virulent or more transmissible – for instance, making a virus airborne or better adapted to different host species. Such research is not necessarily intended for bioweapons development – it’s supposedly intended to help develop vaccines and therapeutics for virus epidemics and for basic research on the behaviour of viruses. But it’s been fiercely criticized for decades by some scientists for posing huge risks to public health in return for little or no benefit.

In fact, the author of the new article does suggest that SARS-CoV-2 was developed as a bioweapon, though he doesn’t suggest that it was deliberately released as one.

The new article, titled, “RaTG13 – the undeniable evidence that the Wuhan coronavirus is man-made”, appears on the “Nerd has Power” blog. The blog site doesn’t identify the author, so we’ll call him or her “Nerd”, and assume he’s male, for the purposes of this article. The article is technical in parts but Nerd does his best to make it accessible to the layperson by explaining every step of his logic, at the same time as giving definitions of scientific terms. In our experience, he succeeds, though non-scientists may need to read the technical parts with close attention, possibly more than once!

The new article brings solid scientific evidence to the row that is raging over the origin of SARS-CoV-2. Some scientists have said that the virus is the result of natural evolution in animal or human hosts. But others have said that while natural emergence is possible, it’s also not possible to rule out a lab escape, either of a natural virus obtained from the wild for research, or even of a genetically engineered virus.

As Nerd points out, all publications arguing for a natural origin for SARS-CoV-2 rely on a single piece of evidence – the sequence of a purported natural bat coronavirus named RaTG13.

RaTG13 looks like a “close cousin” of SARS-CoV-2 – the two are 96% identical throughout the whole sequence of the viral genome. If RaTG13 is a natural virus, SARS-CoV-2 very likely also comes from nature and must share a recent common ancestor with RaTG13. Indeed, it has been argued by those in support of the natural origin of SARS-CoV-2 that the virus arose by the mutation of RaTG13 in animal and/or human hosts.

But there’s one major problem with the natural origin theory, according to Nerd: The RaTG13 virus isn’t real. It doesn’t exist as a “live” sample, only as a sequence of letters in a computer, which only in January this year, after the COVID-19 outbreak hit, was uploaded into a public database. Nerd believes that this sole evidence of its existence, its genetic sequence, was fabricated. And, he says, the major suspect in the fabrication is Shi Zhengli.

We summarise below Nerd’s technical argument that SARS-CoV-2, as originally found in Wuhan, China, was genetically engineered. However, we strongly encourage readers to go to his full article, to look at the graphs that illustrate his argument, and to check out his linked sources.

Nerd’s argument is being taken seriously by many well qualified commentators, both on Twitter and in the Comments section of his original posting here. His updated post, which takes account of comments and corrections he’s received from readers, is here.

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Summary of Nerd’s argument that SARS-CoV-2 is genetically engineered

1) Many mutations in natural evolution are single DNA or RNA nucleotide substitutions; that is, a change of a single base unit (nucleotide) in the order of the base units that constitutes the genetic material of the organism. (Note: The genetic material of coronaviruses is RNA, not DNA.) These random single nucleotide mutations within a protein-coding region of the genetic material of an organism can have one of two outcomes. Either it can have no effect on the genetic code and thus no effect on the order of amino acids in the corresponding protein – this is known as a “synonymous mutation”; or the single nucleotide change can alter the genetic code, leading to a change in the amino acid sequence of the protein for which it encodes, conferring in turn new properties to the protein – this is known as a “non-synonymous mutation”.

2) There are strict rules that govern natural evolution through random single nucleotide mutation. In particular, typically the ratio between the number of synonymous mutations and that of non-synonymous mutations should be around 5:1; that is, 5 times more synonymous mutations than non-synonymous arise through this process. In other words there should be an amino acid change with every 6th single nucleotide mutation.

3) If we consider the natural rates and patterns of mutational changes between two bona fide native bat coronaviruses identified by a lab in China that has a military background, ZC45 and ZXC21, everything is as predicted, in line with what we know about how viruses evolve in nature. The changes are consistent with what is expected when two lineages closely relate to each other evolutionarily and the differences in their sequences are the results of random mutations. The ratio between the number of synonymous mutations and that of non-synonymous mutations is around 5:1.

4) But a comparison between SARS-CoV-2 and its purported close relative RaTG13 shows a pattern that’s completely inconsistent with natural evolution through single nucleotide substitution. The synonymous/non-synonymous mutation ratio is 44:1 – wildly divergent from the 5:1 ratio expected from a natural evolution.

5) Comparing SARS-CoV-2 and RaTG13, the whole spectrum of RNA sequence and amino acids have a very high similarity in every genomic region except in the S2 (Spike 2) half of the spike protein – which is very different. The S2 spike protein region doesn’t follow the evolutionarily predicted and observed frequency of synonymous and non-synonymous mutation rates for coronaviruses. Although there are 90 nucleotide differences there are only two amino acid substitutions rather than the 15 that would be expected. Thus there are far fewer amino acid substitutions compared with what should happen naturally.

6) A safe conclusion to the above points is that, between SARS-CoV-2 and RaTG13, at least one is non-natural. If one is natural, then the other one must not be. It’s also possible that neither of them came from nature.

7) The part of a virus that determines how good it is at infecting humans is the receptor binding domain (RBD) located in the S1 region of the spike protein located on the surface of the virus. The RBD dictates whether or not the virus can bind to the ACE2 receptor on the surface of human cells and thereby infect humans. This is the “business part” of the virus. If it’s not right, it won’t infect humans. If it is right, it will.

8) If indeed RaTG13 is a fabrication, what are the bona fide bat viruses that are most closely related to the Wuhan SARS-CoV-2 virus and thus could be its “parents”? By comparing amino acid and nucleotide sequences, Nerd identifies the two bat coronaviruses reported in the scientific literature, ZC45 and ZXC21, as the closest fits. ZC45 and ZXC21 are also remarkably similar to each other, with a 97% sequence identity.

9) A comparison between the amino acid sequences of the Wuhan SARS-CoV-2 virus as originally described and the ZC45 and ZXC21 viruses shows a remarkable identity in all but one crucial region. In the majority of the virus there is 95% amino acid sequence identity, but there is one crucial region where they are strikingly dissimilar, with only 69% identity. That is the S1 region of the spike protein that harbours the RBD. Given the very high identity in all other regions of the SARS-CoV-2 virus when compared with ZC45 and ZXC21, it is highly improbable that such a huge difference in just the S1 part of the spike protein of SARS-CoV-2 could have arisen naturally over the timespan in which they are supposed to have co-existed in nature.

10) The other striking result of a comparison between SARS-CoV-2 and ZC45/ZXC21 relates to another component, the E protein. The E protein is a structural protein of coronaviruses that can tolerate a large number of mutations without any negative impact on function. This is highlighted by the fact that even after just two months after the outbreak of the COVID-19 pandemic, mutations in the E protein of SARS-CoV-2 were identified. However, when comparing the original SARS-CoV-2 virus with the ZC45/ZXC21 bat viruses, they have a 100% identical E protein amino acid sequence. Given the high mutation rate observed in SARS-CoV-2 (and in coronaviruses in general), and given the fact that mutations can occur anywhere in the virus genome, including in the E protein region, it makes no biological sense that the original SARS-CoV-2 virus would have a 100% identical E protein amino acid sequence to the ZC45/ZXC21 bat viruses.

11) Both the above basic biological observations strongly indicate that the only way that SAS-CoV-2 can be so dissimilar in the S1 region of the spike protein (crucial to human infectivity), yet identical in a far less crucial component such as the E protein, is through intentional design (genetic manipulation in the lab) and not by natural mutation and selection in animal and human hosts.

12) The above information strongly points to SARS-CoV-2 being constructed based on one or both of the two bat viruses, ZC45 and ZXC21, rather than the purported RaTG13.

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Intention

Based on the above information, in GMWatch’s interpretation, the intention of these genetic manipulations would be to determine which amino acid changes are required in the RBD of bat viruses for them to gain infectivity in human cells.

We do not share Nerd’s conclusion that the original SARS-CoV-2 was necessarily developed as a bioweapon, though there’s no proof that it wasn’t. It is equally likely to have been developed for study purposes and/or in order to help develop therapies or vaccines for current or future coronavirus pandemics.

Shi Zhengli’s role

There is also the question of Shi Zhengli’s involvement. Nerd poses a series of questions that must awaken suspicion in anyone familiar with the naked ambition that characterizes the virus gain-of-function area of scientific research.

Nerd asks: If RaTG13 were a bona fide natural bat coronavirus discovered in the wild in 2013, as Shi Zhengli claims, given its "star quality" regarding the high potential to infect humans, why didn’t Shi rush to publish its sequence at the time in a prestigious journal? After all, this is what she had done previously with other bat coronaviruses, Rs3367 and SHC014, which share considerable sequence similarity with SARS. Why did she wait until January 2020, when the public row began about the possible lab origin of SARS-CoV-2, before publishing the sequence?[2]

Nerd’s implication is that, with speculation mounting about the possible lab origin of SARS-CoV-2, and the WIV being a chief suspect, Shi scrambled to come up with some sort of “evidence” to show that the virus had a natural origin and thus was nothing to do with her lab. That “evidence” consisted of the fabricated sequence of RaTG13.

Why 2013?

If we accept Nerd’s conclusion that RaTG13 is a fabrication, why would Shi and her collaborators claim it was discovered way back in 2013,[3] as opposed to more recently? Nerd doesn’t go into this, but GMWatch believes that two possible reasons are:1) To avoid awkward questions about why no live sample of RaTG13 is available, enabling us to confirm its real existence – after all, 2013 is a long time ago.2) To give sufficient time for RaTG13 to plausibly naturally mutate and emerge as SARS-CoV-2, thus supporting the “natural origin” hypothesis for the COVID-19 epidemic.

Why the delay?

GMWatch follows Nerd in finding Shi Zhengli’s delay in publishing the sequence of RaTG13 very curious to say the least and we understand why he regards it as highly suspicious.

In our view, such work, once published, would be universally acclaimed as of immense public health import and potentially worthy of the Nobel Prize. If RaTG13 is real, it’s not the kind of thing that a scientist of Shi’s standing would normally keep under wraps for years. As any scientist can tell you, they are driven by the desire to be the first to announce a new discovery and to bask in the peer recognition and glory that this brings – unless, of course, secrecy was mandated because the plan was to use RaTG13 in some way that could not be disclosed, for example, as the basis for developing a bioweapon.

Personal ambition apart, Shi Zhengli is at fault either way, if RaTG13 is real or if it’s fake.

If RaTG13 is real, Shi’s failure to immediately report this discovery appears to be an act of extreme negligence that has recklessly endangered public health. In accord with proper scientific conduct in the public interest, Shi was morally obliged to promptly announce her discovery of RaTG13 and thus put world health authorities on alert as to the possibility of this bat virus acquiring the relatively few mutations needed to convert it to a human pathogen, thus leading to a new SARS pandemic.

If RaTG13 is fabricated, she would be guilty of scientific fraud, apparently committed to cover up an act of negligence in the form of her lab’s construction and accidental release of SARS-CoV-2.

In our view, the evidence presented above shows that there is an urgent need for a credible and independent international investigation into the origins of SARS-CoV-2 and the roles played by Shi Zhengli, the Chinese government, and the US bodies that helped fund the virus research at the WIV, including the National Institutes of Health and the EcoHealth Alliance.

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Notes

1. Some of our readers have voiced concerns at the fact that we are taking seriously certain evidence (e.g. this) about SARS-CoV-2’s origins despite the fact that it is anonymously authored. While we support full transparency and accountability in science, we understand that powerful interests and strong emotions are involved in the current situation. Therefore we are not surprised that some commentators are afraid to put their names to their views. This may be particularly the case with Nerd, who, judging by his use of Chinese on his blog site, may be a Chinese citizen. In his article, he strongly accuses the “Chinese Communist Party” for responsibility for SARS-CoV-2’s emergence.

Because we want to get the evidence on SARS-CoV-2 out into the open and because we believe that scientists have as much of a right to “stay safe” as the rest of us, we will continue to publish scientific articles on the topic even when the authors feel that they have to remain anonymous.

2. The sequence of BtCoV/4991 RdRp – a fragment of a bat virus genome (370 nucleotides) – was published by Shi Zhengli and colleagues in 2016, four years before RaTG13. As far as the fragment goes, it is identical to the RaTG13 sequence published in Jan 2020. However, this does not affect Nerd’s argument that RaTG13 is a fake.

As the commentator “Simen” says on Nerd’s blog site, “The existence of RaBtCoV/4991 actually does not prove anything. The sequence is only 370bp in length and everything else [was] still not published until 27-JAN-2020.… Notably, if what they claim was true on the S protein, we should [have] already seen the RBD of RaTG13 being published before. We didn't. Therefore, we cannot rule out fabrication/manipulation for the rest of RaTG13/RaBtCoV/4991. Without being able to rule out such fabrication/manipulation, the argument that RaTG13 is invalid as ‘evidence’ for a ‘natural’ origin of SARS-CoV-2 is still… valid….”

It is a mystery as to why Shi and colleagues only published a tiny fragment of this virus genome. The procedure used to obtain the sequence of this RdRp gene fragment would have provided them with the entire sequence of the virus. Thus the rest of the sequence information appears to have been withheld.

3. In a 2016 paper, Shi describes the collection of samples from a mineshaft that led to the isolation of the bat virus BtCoV/4991. Peter Daszak of the EcoHealth Alliance has stated on Twitter that BtCoV/4991 is the same virus from the same sample as RaTG13.